Pronounced health disparities associated with race and socioeconomic status (SES) are noted for brain health endpoints including stroke (particularly at younger ages), dementia, brain structure on magnetic resonance imaging (MRI), cognitive decline, and functional disability. Efforts are needed to disentangle respective influences of race and SES on brain health, particularly early and subtle markers of pathology predictive of future stroke and dementia. MRI- assessed measures of gray matter (GM) and white matter (WM) volume and diffusion tensor imaging measures of WM microstructure offer such proven associations. Also critical is identification of multi-level mediators of the relations of race and SES to subtle brain pathology. Biomedical, behavioral, psychological, social and environmental factors have been implicated as potential mediators of the relations of race and SES to many physical health outcomes, but exceedingly little is known about these pathways with respect to brain health. MRI indices of subtle brain pathology may also mediate relations of race and SES to cognitive and physical function. Here we propose an interdisciplinary, ancillary study to the Healthy Aging In Neighborhoods of Diversity Across the Life Span (HANDLS). HANDLS study is a new 20-year epidemiological investigation conducted by the National Institute on Aging's Intramural Research Program focused on understanding health disparities among 4,000 socioeconomically diverse African-Americans (AA) and Whites living in Baltimore, MD. HANDLS is uniquely designed to disentangle the respective relations of race and SES to health outcomes. In HANDLS SCAN we propose to obtain quantitative MRI data from 500 (250 AA, 250 White; ages 30-64) stroke- and dementia-free HANDLS participants with a full range of SES to: (1) Examine race- and SES-related disparities in GM and WM volume, and WM microstructure (2) Examine multi-level mediators - biomedical, behavioral, psychological, social, and environmental - of the relations of race and SES to GM and WM; and (3) Examine whether GM and WM are proximal mediators of the relations of race and SES to cognitive and physical function. Structural equation modeling will be used to construct increasingly complex models to address these interrelated aims. PUBLIC HEALTH RELEVANCE: An understanding of multi-level mediators of the relations of race and SES to early and subtle markers of brain pathology, and the relation of brain pathology to cognitive and physical function, is needed to facilitate appropriate strategies in prevention and intervention critical to the reduction and ultimate elimination of health disparities in stroke, dementia, and cognitive and functional decline.